Snippets

Vantage Snippets are short summaries of breaking news stories.

Early data boost Aslan, but don’t ignore the red flags

Data in only 18 patients from a project with limited patent life, a partner owed millions down the road and a hugely competitive target market: this being 2021, what’s not to like? Thus shares in Aslan jumped 65% in pre-market trading on hopes for ASLAN004 in atopic dermatitis; the level of efficacy reported certainly makes the project desirable, assuming that it is confirmed in larger trials. Results in a further 16 patients are due mid-2021, with a much larger phase IIb slated for later this year. Efficacy is not the only appeal here: Aslan is striking for once-monthly dosing and hopes that ‘004 will show lower rates of conjunctivitis than Sanofi/Regeneron’s mega-blockbuster Dupixent, which is given every two weeks. The two MAbs are mechanistically very similar, but subtle differences in receptor binding could hold the key to these important differentiations, the company believes. The downsides: ‘004’s inventor CSL is owed considerable milestone payments, and the project’s composition of matter patent expires in 2027. Throw in an incredibly crowded dermatitis space, and is not surprising that Aslan’s roar faded to a 19% share price rise by mid-morning.

Disclosed terms of Aslan-CSL deal
Milestone  Cost to Aslan
Commencement of phase III $30m
Regulatory milestones up to $95m
Sales milestones  up to $655m
Royalties on net sales  mid-single digit to 10%
Note: research deal first signed in 2014, amended to full global licensing deal in 2019. CSL's consent is also needed over any change of control. 

Note: selected doses only; *phase IIb trial; **results at wk 12;  ^phase I trial, results at wk 8, per protocol, 7 patients lost to Covid-19 restrictions and other reasons, ITT estimated at 50% and 40% respectively.

US FDA approval tracker February

Backed by a positive panel meeting Johnson & Johnson’s JNJ-78436735 became the third Covid-19 vaccine granted US emergency use authorisation (EUA), but it is the first that requires only one dose. The company plans to deliver 100 million doses to the US during the first half of the year. An EUA was also granted to Lilly’s bamlanivimab plus etesevimab after the antibody combo significantly cut Covid-19-related hospitalisations and deaths in studies. February saw Bristol Myers Squibb’s Breyanzi become the third anti-CD19 Car-T therapy approved, and the project’s efficacy looks on a par with Gilead’s Yescarta, with less toxicity. However, Breyanzi is even more expensive to manufacture than existing Car-T products. Novartis’s Entresto gained approval in a broad heart failure population, but the group will need to make the most of this before generic competition hits. And Athenex had a knockback for Oraxol, a combination of oral paclitaxel and encequidar, in metastatic breast cancer. The FDA cited toxicity concerns and requested another clinical study. The Pdufa was scheduled for the last day of February and the news, released today, knocked half a billion dollars off the company's market cap.

Notable first-time US approval decisions in February
Project Company 2026e sales by indication ($m) Outcome
Breyanzi (liso-cel) Bristol Myers Squibb 1,096 Approved
Oraxol (oral paclitaxel + encequidar) Athenex 781 CRL
Cosela (trilaciclib) G1 Therapeutics 583 Approved
Tepmetko (tepotinib) Merck KGaA 505 Approved
Pepaxto (melphalan flufenamide/melflufen) Oncopeptides 490 Approved
Ukoniq (umbralisib) TG Therapeutics 296 Approved*
Defencath/Neutrolin Cormedix 230 CRL
Amondys 45 (casimersen) Sarepta 202 Approved
Posimir Durect 195 Approved
StrataGraft Mallinckrodt 59 Deferred (manufacturing inspection)
Nulibry (fosdenopterin) Bridgebio 29 Approved
Evkeeza (evinacumab) Sanofi/Regeneron - Approved
*Gained approval in marginal zone lymphoma and follicular lymphoma. Sources: EvaluatePharma & company releases.
 
 
Advisory committee meetings in February
Project Company 2026e sales by indication ($m) Outcome
Keytruda Merck & Co 3,943* Negative, 10-0 (neoadjuvant/adjuvant use in triple-negative breast cancer)
*SBI includes the approved use in triple-negative breast cancer in combination with chemotherapy. Sources: EvaluatePharma & company releases. 
 
 
FDA issued EUAs to treat Covid-19
Project Company 2026e sales by indication ($m) Setting
Bamlanivimab + etesevimab Lilly 303 Treatment of mild to moderate Covid-19 in adults and paediatric patients aged 12 and over
Ad26.COV2.S
(JNJ-78436735)
Johnson & Johnson -* Prevention of Covid-19 (after positive adcom also in February)
*Consensus not yet available. Sources: FDA.gov & EvaluatePharma
 
 
Supplementary and other notable approval decisions in February
Product Company Indication (clinical trial) Outcome
Gocovri Adamas Off episodes in Parkinson's disease patients receiving levodopa-based therapy Approved
Plegridy (intramuscular) Biogen Relapsing-remitting MS Approved
Libtayo Sanofi/Regeneron NSCLC with ≥50% PD-L1 expression (Empower-Lung-1) Approved
Vazalore Plx Pharma Liquid-filled aspirin capsule (325mg and 81mg doses) No decision yet
Entresto Novartis Heart failure with preserved ejection fraction (Paragon HF Approved
Rapivab Biocryst Acute uncomplicated influenza to include patients six months and older Approved
Libtayo Sanofi/Regeneron Full approval in locally advanced basal cell carcinoma and accelerated approval in metastatic BCC (NCT03132636) Approved
Panzyga Pfizer Chronic inflammatory demyelinating polyneuropathy (NCT02638207) Approved
Humira Abbvie Paediatric patients with moderate to severe ulcerative colitis (Envision I) Approved
Sources: EvaluatePharma & company releases.

Teon claims an adenosine pathway, but it’s not alone

Interest in adenosine’s role in cancer is growing, and one of the latest in on the act is Teon Therapeutics, a private US biotech that last week closed a $30m series A financing round. The group first floated the possibility of collaborating with Cancer Research UK in December, and today said a deal had been signed: CRUK is to sponsor a phase I/II trial of Teon’s adenosine A2B receptor antagonist TT-702 in cancers including prostate and triple-negative breast. Teon calls TT-702 a “first-in-class” small molecule, though this claim does not stand up to scrutiny. Spain’s Palobiofarma has a pipeline of adenosine antagonists that includes the A2B-specific molecule PBF-1129, which is in two phase I trials in lung and other solid tumours. And Gilead’s 2020 deal with Arcus includes etrumadenant, an inhibitor active at A2A and A2B receptors and already in phase II for NSCLC. Adenosine receptors are overexpressed on some cancers, and a role for the A2B subtype in tumour cell proliferation has recently been proposed. Teon says it will have to pay an undisclosed amount to CRUK in return for rights to the TT-702 data generated.

Selected adenosine A2B receptor antagonists
Project Company Status Detail
Etrumadenant* Arcus/Gilead Phase II Zimberelimab + domvanalimab combo in NSCLC
PBF-1129 Palobiofarma Phase I Monotherapy in NSCLC 
TT-702 Teon Therapeutics Preclinical CRUK-sponsored ph1/2 study in pancreatic cancer & TNBC to start 2021
A2A & A2B antagonist* Adorx Therapeutics Preclinical
LNC-002 Inspyr Therapeutics Preclinical Likely inactive project
GS 6201 Gilead (ex CV Therapeutics) Discontinued
Source: EvaluatePharma; *also said to be active at the A2A subtype.

Novocure finds timing inopportune for Optune

With its electrical field-emitting Optune device, Novocure has achieved something biotech has repeatedly failed to do: improve the survival of glioblastoma patients. A different version of the device, Optune Lua, is also approved for mesothelioma. Efforts to extend into other cancers, however, have hit a snag, with the company yesterday admitting that several clinical trial readouts would be delayed by Covid-19. Most important of these is Panova-3, the pivotal trial of Optune in pancreatic cancer, whose readout has been pushed back a year. The 14% fall in Novocure’s share price yesterday, though, was also to do with the glioblastoma indication. Medicare coverage for the use of Optune to treat the brain cancer had initially been denied; a reversal of this decision in 2019 has allowed Novocure to appeal previously denied claims, creating a backlog of payments and swelling the group’s top and bottom lines. This backlog has now been pretty much exhausted, so many analysts expect Novocure’s sales to grow much more slowly in the coming years. R&D expenses are also taking their toll, with the company sponsoring an astonishing 34 active clinical trials, 26 of which are in brain tumours. 

Selected upcoming Optune trial readouts
Trial Details N Readout
Hepanova Pilot ph2 in advanced liver cancer 25 Final data Q2 2021 (delayed from Q1)
Innovate-3 Pivotal ph3 in recurrent ovarian cancer 540 Interim data Q3 2021; final data 2023
Lunar Pivotal ph3 in NSCLC 534 Interim data Q4 2021; final data 2023
EF-31 Pilot ph2 in gastric cancer 28 Final data 2022 (delayed from 2021)
Metis Pivotal ph3 in brain mets from lung cancer 270 Final data 2022
EF-33 Pilot ph2 of high-intensity arrays in recurrent glioblastoma  25 Final data 2022
Panova-3 Pivotal ph3 in pancreatic cancer 556 Interim data 2022 (delayed from 2021); final data 2023
Source: EvaluateMedTech & company release.

Sarepta gains credibility, but confirmation is still three years away

With Sarepta already running a confirmatory trial of its third exon-skipping Duchenne muscular dystrophy therapy, its US accelerated approval last night perhaps lacked the drama of earlier green lights. Moreover, though the label of the drug now branded Amondys 45 is backed by a surrogate endpoint, dystrophin expression, there is a placebo comparator. In this regard Sarepta is gaining credibility: its first two DMD exon skippers, Exondys 51 and Vyondys 53, got accelerated approvals based on small, uncontrolled studies. The former’s confirmatory trial did not even start for another four years, and the latter had to contend with a complete response letter. The Essence study will seek to confirm the approvals of Vyondys and Amondys alike, and Amondys’s conditional green light is backed by early data from this same trial. If Sarepta dragged its feet it was not alone: US data show that, of 23 accelerated approvals granted in 2010-20 to non-oncology drugs, only four had converted to full approvals through clinical confirmation as at the end of 2020, taking an average of 3.5 years to do so. And as-yet unconverted accelerated approvals for Makena, Ferriprox and Sirturo date back to 2011-12.

Sarepta's accelerated approvals
        Confirmatory trial
Drug 2026e sales ($m) Accelerated approval basis Approval Name & start Data?
Exondys 51 442 6min walk test in 2 trials (n=12), vs external controls, & dystrophin expression Sep 2016 MIS51ON, mid-2020 2026
Vyondys 53 243 Dystrophin expression in 1 trial (n=25) Dec 2019 Essence, mid-2016 2024
Amondys 45 202 Dystrophin expression in Essence trial (n=27), vs placebo Feb 2021 Essence, mid-2016 2024
Source: EvaluatePharma & clinicaltrials.gov.

Bluebird sings to a select group of investors

Bluebird’s exclusive disclosure yesterday regarding two crucially important cancer cases that this month caused Lentiglobin clinical trials to be halted sent its stock up 8%. This is great news, therefore – unless you happen not to have registered for the investor conference where the bombshell was dropped. The revelations concerned further analysis of Lentiglobin’s phase I/II sickle cell disease trial, where one subject had developed acute myeloid leukaemia and another myelodysplastic syndrome. They were made at yesterday’s SVB Leerink healthcare conference rather than in a regulatory filing, flying in the face of the company’s promise 10 days ago to be transparent. The gist is that both patients had had very severe sickle cell disease, that the AML might have occurred independently of the vector that delivers Lentiglobin, and that the MDS might not have been MDS at all. Bluebird is continuing its investigation, and the complete analysis of the AML case could now come in a couple of weeks. Yesterday the company’s chief executive, Nick Leschly, said: “We are going to be as transparent as we can be with all stakeholders.” All investors really deserve better.

Two suspected unexpected serious adverse reactions in the HGB-206 sickle cell trial
Case What the markets learned on 16 Feb… …and what (some) investors found out on 25 Feb
AML Occurred >5yrs after dosing; vector detected in patient’s tumour cells, but unclear whether it was “passenger” or "driver"; work needed to investigate whether vector was inserted near oncogenic genes, and whether these were upregulated Patient determined to have chromosomal abnormalities including monosomy 7, partial loss of the short arm of chromosome 11, mutations in RUNX1 and PTPN11; these known AML driver mutations suggest independent mechanism for occurrence of AML
MDS Occurred ~6mth after dosing; not ascertained whether tumour cells were carrying vector; patient had genetic abnormality, trisomy 8, seen in 10-15% of MDS cases, suggesting underlying risk factors No occurrence of blasts or dysplasia in the bone marrow, which suggests that patient might not, in fact, have met criteria for diagnosis of MDS; patient had prolonged anaemia with trisomy 8 and tetraploidy
Source: Bluebird Bio.

Hints of a quickening emerge in accelerated approval conversions

The number of US approvals via the accelerated pathway has soared in recent years, particularly in oncology, recent Evaluate Vantage analyses have shown. And there are hints that conversions to full approval are accelerating, as suggested by the chart below. Still, two thirds of the 130 drugs approved on an accelerated basis in the last decade have yet to be converted, and more energy could be expended by the agency and sponsors alike. The data reveal some of the worst offenders, with Amag’s Makena, now owned by Covis, an extreme example. The FDA has proposed withdrawing the controversial preterm birth treatment, but foot-dragging by its owners means that it is still available. It is also notable that Tykerb and Istodax were both commercial flops, while the likes of Imbruvica and Alimta went on to become huge blockbusters. This is not to say that time to convert is always correlated with success; Imbruvica has three accelerated approvals outstanding, the first won seven and a half years ago.

The best of times and the worst of times
Product and sponsor  Setting (year of accelerated approval)  Time to convert to full approval
Quick turnarounds…
Imbruvica - Pharmacyclics* Relapsed/refractory chronic lymphocytic leukaemia (2014)  166 days 
Alimta - Lilly  1st-line non-squamous NSCLC (2018)  240 days
Jadenu Sprinkle - Novartis  Iron overload caused by blood transfusions (2017)  358 days
Took their time…
Tykerb - Glaxosmithkline** 1st-line Her2 +ve breast cancer (2010)  8.9 years
Exjade - Novartis  Iron overload in certain thalassaemia patients (2013)  7.5 years
Adcetris - Seagen Relapsed/refractory anaplastic large cell lymphoma (2011)  6.6 years
Hall of shame… 
Makena - Amag^ To reduce the risk of preterm birth (2011)  10 years and still waiting 
Istodax - Celgene^^ Relapsed/refractory peripheral T-cell lymphoma (2011)  Almost 10 years and still waiting
Ferriprox - Chiesi Iron overload in thalassaemia patients in need of additional chelation (2011)  9.5 years and still waiting
*Now owned by J&J/Abbvie; **Now owned by Novartis; ^Now owned by Covis; ^^Now owned by Bristol Myers Squibb. Source: FDA.gov. 

The Covid-19 valuation derby

Last week Evaluate Vantage looked at the biggest one-day share price moves caused by Covid-19-related activities. An examination of the biggest one-day gainers in terms of market cap, using EvaluatePharma’s EventAnalyzer, reveals a similarly startling picture. Some of these gigantic moves occurred for sensible reasons: it is hard to argue with the importance of the superb pivotal trial data on Moderna’s Covid-19 vaccine, for instance. Others, such as Gilead’s decision to start trials of remdesivir resulting in a $5.8bn valuation bump, and Regeneron adding $4.2bn simply because its antibody doublet was used to treat a hospitalised Donald Trump, are rather more preposterous. It is notable that the market cap of these last two companies subsequently dropped by $14bn apiece. It should also be mentioned that two of the movers in the table below, Abcellera and Curevac, recorded much bigger one-day market cap rises – of $10.3bn and $6.6bn respectively – on their first days as public companies. While these gains cannot be specifically attributed to Covid-19, enthusiasm for companies active in this space will certainly have played a part. 

The biggest one-day market cap moves prompted by Covid-19 announcements
Company  Event  MC rise ($bn) Resulting MC ($bn) Current MC ($bn)
Moderna Nov 30, 2020: topline data from phase III Cove study show mRNA-1273 is 94% effective in preventing Covid-19 10.2 60.4 63.0
Biontech Mar 17, 2020: company to collaborate with Pfizer on the Covid-19 vaccine candidate BNT162* 6.0 15.1 27.6
Gilead Sciences Feb 26, 2020: company starts two phase III studies of its antiviral remdesivir for Covid-19 5.8 94.5 80.4
Novavax Jan 28, 2021 [post market]: topline data from UK phase III study show NVX-CoV2373 is 89.3% effective in preventing Covid-19 5.5 14.1 15.6
Moderna May 18, 2020: data from phase I study show mRNA-1273 produced neutralising antibodies in all eight initial participants 4.9 29.7 63.0
Regeneron Pharmaceuticals Oct 2, 2020 [post market]: company's Covid-19 antibody REGN-COV2 is used to treat then-President Donald Trump 4.2 63.3 49.3
Curevac Nov 16, 2020: European Commission to buy up to 450 million doses of the company's Covid-19 vaccine CVnCoV 1.9 15.2 19.2
Vir Biotechnology Feb 26, 2020: shares rise for a second day after company signs deal with Wuxi Biologics to develop antibodies to treat Covid-19* 1.5 3.8 8.8
Abcellera Biologics Jan 28, 2021: Company's partner Lilly will study its antibody bamlanivimab in combination with VIR-7831 in Covid-19 1.2 13.7 10.7
Mesoblast Apr 23, 2020 [post market]: company's stem cell therapy remestemcel-L shows 83% survival in ventilator-dependent Covid-19 patients 1.0 1.7 1.2
*Note: Biontech added a further $5.8bn in market cap a day later. Vir added $304m the previous day. Analysis excludes big pharma. Source: EvaluatePharma & company releases.

Brainstorm’s go or no-go decision

Brainstorm Cell Therapeutics is today facing a monumental decision: quit all developmental work on its lead asset in its most advanced indication or press on with a regulatory filing despite a dire warning from the US FDA on the project's chances of success. However, this might feel like déjà vu for investors. Back in November Brainstorm decided to try to file its autologous cell therapy treatment NurOwn in ALS despite the unequivocal failure of its pivotal trial. Today the agency made its position clear, stating that the clinical data Brainstorm has submitted did not meet its threshold for filing. However, in what must be an acknowledgement of what a terrible disease ALS is, the agency did not preclude Brainstorm from proceeding with a BLA submission. But, even with the support of patient groups desperate for a cure, it is hard to see how Brainstorm will succeed without further clinical trials and, with only $42m in the bank, funding those trials and its other work in multiple sclerosis might be a struggle. However, while Brainstorm’s next move might be slightly opaque, investors were very clear where they stood, with shares falling by 30% in early trading today.

Immunome soars 76% on Covid-19 hopes – but that's nothing

Shares in Immunome jumped 76% yesterday after the company claimed to have isolated “potent antibodies” capable of neutralising several worrying SARS-CoV-2 variants, the result of very early discovery work that in today’s market is apparently worth $177m. This is far from the most egregious valuation surge triggered by Covid-19 claims, however, examples of which can be found from the very start of the pandemic. EvaluatePharma’s EventAnalyzer helps pinpoint some of the biggest percentage one-day gains seen over the past 12 months. Almost all of these groups used the opportunity to raise money, and most have failed to deliver on hopes. Ocugen stands out as a big beneficiary, for now at least. The company was a penny stock a mere 10 weeks ago, and executives were poised to ask shareholders to agree to a painful reverse split to prevent the stock’s banishment from Nasdaq. A deal with the Indian vaccines group Bharat Biotech changed its fortunes, and the initial near tripling of Ocugen’s shares was only the beginning of the gains. This is an exception rather than the rule, of course, something that those chasing Immunome yesterday would do well to remember.

Chasing cures: the biggest one-day share price moves prompted by Covid-19 announcements
Company  Event  Share price rise (%) Resulting market cap ($m) Current market cap ($m)
Equillium Jul 13, 2020: partner Biocon claims a mortality benefit in 30-patient trial of itolizumab, used to treat cytokine release syndrome in hospitalised Covid-19 patients 731% 469 268
Bellerophon Therapeutics Mar 20, 2020: FDA grants emergency expanded access to company's inhaled nitric oxide delivery system INOpulse for treating Covid-19 431% 82 75
Synairgen Jul 21, 2020: data from a 101-patient phase II trial show 79% reduction in risk of severe disease with SNG001 vs placebo 421% 349 367
Capricor Therapeutics Apr 29, 2020: 6 of 6 patients with acute respiratory distress syndrome caused by Covid-19, treated with cardiac cell therapy CAP-1002, survived, and four recovered 253% 76 148
Immuron Jul 21, 2020: company claims that its IMM-124E technology is active against Covid-19 virus, in preclinical experiments 249% 99 53
Gritstone Oncology Jan 19, 2021: company starts phase I trial of second-generation Covid-19 vaccine intended to protect against mutant variants 249% 841 694
AIM Immunotech Mar 9, 2020: Japan starts testing company's chronic fatigue drug Ampligen, in Covid-19 191% 135 101
Ibio Feb 28, 2020: files to raise $100m in the wake of deal with CC-Pharming to develop and produce Covid-19 vaccine candidates 183% 187 442
Ocugen  Dec 12, 2020: signs US development and commercialisation deal with Bharat Biotech over the Indian group's Covid-19 vaccine candidate Covaxin  174% 130 1,900
Tiziana Life Sciences Mar 11, 2020: company says it plans to put its preclinical anti-IL-6 project TZLS-501 into Covid-19 trials 166% 152 311
Note: excludes companies with a market cap move of less than $35m. Source: EvaluatePharma & company releases.
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